Drug & supplement interaction

Kava + Conjugated Estrogens, Methyltestosterone

Conjugated Estrogens, Methyltestosterone brand name: Premarin with Methyltestosterone.

Moderate Interaction
The bottom line Moderate

Conjugated Estrogens, Methyltestosterone falls into 3 drug categories that Kava can interact with; the most serious is rated moderate. Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Conjugated Estrogens, Methyltestosterone

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Kava interacts with whole categories of medication. Conjugated Estrogens, Methyltestosterone falls into 3 of those categories, so it can interact with Kava in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 3

Why this applies to Conjugated Estrogens, Methyltestosterone

Conjugated Estrogens, Methyltestosterone falls under HEPATOTOXIC DRUGS — the group Kava interacts with.

Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.
Kava has been linked with over 100 cases of hepatotoxicity. Most cases occur with excessive and prolonged use. There is some concern that kava can adversely affect the liver, especially when used in combination with hepatotoxic drugs.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with kava and your Premarin with Methyltestosterone combo. This isn't about kava changing how the medicine works. It's about the liver. Kava has been tied to rare but real liver injury, and methyltestosterone (an oral anabolic-type hormone) is also known to be hard on the liver. When you stack two things that can stress the same organ, the worry is that the combined load could raise your risk of liver problems.

To be fair, this concern is mostly theoretical and based on scattered case reports, not strong studies. Still, it's worth watching for warning signs like yellowing of the skin or eyes, dark urine, belly pain, or unusual fatigue. Please check with your pharmacist or doctor before combining these, and don't stop anything on your own.

References
  1. Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ 2001;322:139.
  2. Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity [letter]. Ann Intern Med 2001;135:68-9.
  3. Liver Toxicity With Kava. Pharmacist's Letter/Prescriber's Letter. January 2001.
  4. Consultation letter MLX 286: Proposals to prohibit the herbal ingredient Kava-Kava (Piper methysticum) in unlicensed medicines. Medicines Control Agency, United Kingdom, July 19, 2002.
  5. Li XZ, Ramzan I. Role of ethanol in kava hepatotoxicity. Phytother Res 2010;24:475-80. PubMed
  6. Chanwai, L. G. Kava toxicity. Emergency Medicine 2002;12:142-145.
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 3

Conjugated Estrogens, Methyltestosterone also falls under P-GLYCOPROTEIN SUBSTRATES.

It is unclear if kava inhibits P-glycoprotein (P-gp); research is conflicting.
In vitro research shows that kava can inhibit P-gp efflux. However, a clinical study in healthy volunteers shows that taking kava standardized to provide 225 mg kavalactones daily for 14 days does not affect the pharmacokinetics of digoxin, a P-gp substrate. It is possible that the use of other P-gp substrates or higher doses of kava might still inhibit P-gp.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the honest picture: this concern is about a transporter called P-glycoprotein, which acts like a pump moving certain medicines in and out of cells. Lab dish studies hint that kava might slow that pump, which in theory could let a little more of your hormone medication stay in your body. If that happened, you might notice more of the usual estrogen and testosterone effects, like breast tenderness, fluid retention, mood shifts, or acne.

But the evidence here is weak. A human study using a standardized kava dose showed no real change with another pump-dependent drug. So for most people this is more theoretical than proven. The bigger thing I'd flag is that kava itself can stress the liver, which is also where your hormones are processed, so please check with your pharmacist or doctor before combining them.

References
  1. Weiss J, Sauer A, Frank A, Unger M. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos 2005;33:1580-3. PubMed
  2. Gurley BJ, Swain A, Barone GW, et al. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 2007;35:240-5. PubMed
  3. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Conjugated Estrogens, Methyltestosterone also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

It is unclear if kava inhibits CYP3AA; research is conflicting.
Although in vitro research suggests that kava inhibits CYP3A4, more robust clinical evidence shows that kava has no effect on CYP3A4. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP3A4 activity.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for your Premarin with Methyltestosterone combo. Both the estrogen and methyltestosterone are processed by a liver enzyme called CYP3A4. In a test tube, kava looked like it might slow that enzyme down, which could in theory let hormone levels build up a bit. But when researchers actually tested kava in real people for 28 days, it didn't change CYP3A4 activity at all. So this concern is mostly lab-based and rated as minor and unlikely.

One thing I'd flag more strongly: both kava and this hormone product can stress the liver. Since kava has been linked to rare liver damage, I'd talk with your pharmacist or doctor before combining them, and watch for yellowing skin, dark urine, or belly pain.

References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Kava Also Interacts With Other Medications

Kava has 248 major, 576 moderate, 341 minor known drug interactions in our database — the Conjugated Estrogens, Methyltestosterone one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Kava

Covers the 2,830 medications we’ve checked against Kava. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Conjugated Estrogens, Methyltestosterone

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Conjugated Estrogens, Methyltestosterone page lists 226 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 184 moderate · 36 minor.

From our pharmacist’s overview on the Conjugated Estrogens, Methyltestosterone page

“If you take conjugated estrogens with methyltestosterone (Premarin with Methyltestosterone), a hormone combination used for menopausal symptoms, read the six major-rated entries here before adding any supplement. Most of the 226 ingredients on file change how your body handles the hormones themselves.”

Reviewed by 2 · Jul 18, 2026

Open the Conjugated Estrogens, Methyltestosterone interaction page

One more smart check

Taking Kava as Part of a Dietary Supplement Product? Check It for Interactions

We hold 403 real supplement products containing Kava, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kava. Your product may carry other ingredients that interact with Conjugated Estrogens, Methyltestosterone too, on top of Kava — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Kava and Conjugated Estrogens, Methyltestosterone Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Kava
Top 25%

#285 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Conjugated Estrogens, Methyltestosterone
Top half

#850 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Kava

What is Kava?

Kava
  • Anxiety and stress
  • Restlessness
  • Trouble sleeping
  • Relaxation in social or cultural settings
  • Menopausal symptoms

Kava is a Pacific Island plant traditionally used to promote relaxation and ease anxiety, and some studies suggest it may help mild anxiety. However, kava has been linked to rare but serious liver damage, so it should be used with caution, avoided by people with liver problems, and only used after talking with your pharmacist or doctor.

Read the full Kava monograph & all interactions
Keep checking

Other Drugs & Kava

Browse every other medication we’ve checked against Kava — both the ones with a known interaction and the ones without. Select any drug for the full detail.

248Major
576Moderate
341Minor
1,664No known interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the Kava page.

Moderate

576 interactions

Showing 60 of 576 moderate interactions — see all 576 on the Kava page.

Minor

341 interactions

Showing 60 of 341 minor interactions — see all 341 on the Kava page.

No interaction 1,664 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Kava and Conjugated Estrogens, Methyltestosterone Together: Common Questions

Can you take Kava with Conjugated Estrogens, Methyltestosterone?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Kava and Conjugated Estrogens, Methyltestosterone?
Conjugated Estrogens, Methyltestosterone belongs to more than one drug category, and Kava interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Kava and Conjugated Estrogens, Methyltestosterone interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.